Cell-bound, membrane-spanning receptors provide a means of communication between cells and the extracellular environment. Signals from outside the cell are carried by ligands specific for each particular receptor type. Binding of the ligand to its specific receptor causes a signal to be transmitted by the receptor to the intracellular space, initiating a series of intracellular processes resulting in specific biological effects. We are using the two principal families of single-pass transmembrane receptors to study the basis of receptor specificity and ligand-induced receptor activation by determining the crystal structures of complexes between ligands and their extracellular receptor domains.